510
chapter
22
Metabolic Homeostasis
released from the intestine are metabolized by the liver.
The liver carries out
1. Formation of other molecules from amino acid
precursors, e.g., nonessential amino acids, purines,
pyrimidines, porphyrins, and plasma proteins (such as
albumin, VLDL, and transferrin), for its needs and
those of other tissues;
2. Utilization of the amino acid carbon skeletons in
gluconeogenesis or glycogen or lipid synthesis', and
3. Formation of urea.
After a protein meal, the plasma amino acids are those
delivered from the intestine and those synthesized by the
liver. The levels of branched-chain amino acids are greatly
increased because they bypass the liver, reaching a peak
at about 4 hours and returning to normal by 8-10 hours.
They account for up to 60% of the total amino acids
entering the systemic circulation. After uptake by skele-
tal muscle and transamination, followed by oxidation of
the cy-keto acid derivatives by the pathways described
in Chapter 17, they can meet most energy requirements
of muscle. The branched-chain amino acids have been
called
amino fats.
Their a-amino nitrogen is converted
to alanine, which is transported to liver for elimination
as urea. Figure 22-23 summarizes the various pathways
for amino acids following protein ingestion. Alanine is
formed in intestine and muscle from many of the amino
acids.
Following a protein meal, insulin secretion increases,
which stimulates peripheral tissue uptake of amino acids
and net protein synthesis. On a diet high in carbohy-
drate and low in protein, insulin levels are elevated and
glucagon levels are depressed. On a diet high in protein
and low in carbohydrate, insulin and glucagon levels are
elevated. While amino acids and glucose stimulate in-
sulin release, amino acids stimulate and glucose inhibits
glucagon release. Thus, on a high-carbohydrate diet, in-
sulin promotes hepatic and peripheral tissue utilization
of glucose without the need for hepatic gluconeogenesis.
Because of the low level of glucagon, hepatic glucose for-
mation is depressed. On a high-protein, low-carbohydrate
diet, insulin secretion is stimulated by amino acids and
results in their uptake by peripheral tissue and utiliza-
tion for glucose uptake. However, glucose homeostasis is
maintained because glucagon stimulates hepatic glucose
release.
Protein Catabolism during Starvation
During starvation, following depletion of hepatic glyco-
gen, amino acids become the major source for glucose
homeostasis because of the decrease in plasma insulin
F I G U R E 2 2 - 2 3
Amino acid metabolism following dietary protein intake. Digestion of
protein produces amino acids. Within the intestinal cell, amino acid
interconversions form alanine, which is delivered by the portal blood to
liver, where it serves as the source of cr-amino nitrogen and pyruvate,
which is converted to lipid and glucose. Excess nitrogen is converted to
urea. Branched-chain amino acids (BCAAs) are not taken up by the liver
but enter peripheral tissues such as muscle where they serve as an
important fuel source. Their a-amino nitrogen is transported to liver in the
form of alanine.
level and the rise in glucocorticoid level. The pattern of
amino acids released by skeletal muscle during starvation
does not reflect the composition of muscle protein. Ala-
nine and glutamine account for over half of the amino acids
released. Alanine is taken up by liver, its carbon chain con-
verted to glucose, and the nitrogen to urea. In early star-
vation, the principal site of glutamine metabolism is the
gut. One product is alanine. The special role of glutamine
in gut may be due to the high demand for glutamine in
purine synthesis because of the active shedding of intesti-
nal cells. In long-term starvation, a major site of glutamine
metabolism is the kidney, since the excretion of ketone
bodies requires NH
4
as a counterion formed from ammo-
nia produced by glutaminase. The resulting glutamate is
